Factors that modify tissue responses to chemical carcinogens in different organ systems are studied to evaluate their contribution to changing susceptibilities to carcinogenesis in certain tissues during prenatal and postnatal development. Tissues and organ systems currently under study include the nervous system, kidneys, and liver. Modifying processes now being studied include excision repair of DNA, DNA repair mediated by alkyl acceptor protein (AAP), the changing cellular susceptibility to carcinogens during different stages of the cell cycle, and material vs. fetal metabolism in the bioactivation of transplacental carcinogens. An assay for functional repair of DNA damaged by mutagenic and carcinogenic agents or rendered partially apurinic by mild acid hydrolysis has been improved. In vitro repair of lac operon-containing bacteriophage DNA, using 30,000 x g supernatants from wild type E. coli plus all four deoxyribonucleoside triphosphates has been accomplished and is being extended to the use of comparable homogenates of fetal tissues and dissociated specific cell types to explore ontogeny of DNA capacity during prenatal development. Formation of 06 and N7 methylguanine adducts in DNA of fetal and maternal tissues from gravid rats given the transplacental carcinogen, procarbazine, but not in neonatal rats injected directly, provides evidence that maternal metabolic activation of the carcinogen is crucial for transplacental carcinogenesis by this agent.